Device, System and Process for Modification or Concentration of Cell-Depleted Fluid
a technology of cell-depleted fluid and filtration system, which is applied in the field of filtration system, can solve the problems of clogging of membranes, rapid blockage of membranes, and clogging of dead cells,
Active Publication Date: 2017-01-05
REPLIGEN CORP
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- Description
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- Application Information
AI Technical Summary
Benefits of technology
The system effectively prevents clogging, supports scalable and homogeneous continuous perfusion cultures, enhances productivity, and improves the reproducibility of biological products by ensuring efficient fluid exchange and sterility, facilitating easier monitoring and modification of culture conditions.
Problems solved by technology
Filter chemistries, configurations and modalities of use have been developed to facilitate separation of materials according to their chemical and physical properties; In spite the extensive developments in filter technology, they are generally limited by their tendency to clog; for example, when used to filter a suspension of cultured mammalian cells they tend to clog with dead cells, cell debris, aggregates, fibrous biomolecules or other constituents found in the complex “soup” of a culture.
Debris rapidly accumulates at the surface resulting in rapid blockage of the membrane.
Any accumulation of debris is effectively removed by the “washout” effect of the circulating fluid; nevertheless, one of its limitations is the tendency to form a gelatinous deposit on the filter surface, which may limit the effectiveness of the filter and eventually clogging it.
If a change in flow direction is described using a complex pathway of tubing, valves and pumps, placement of such components in a culture flow path adds sheer to the system and provides sites for cell to aggregate and potential clogging sites, nor are such systems very amenable for sustaining homogeneous cultures.
That system, however, is limited in its range of applications.
While several methods have been developed to optimize batch culture production, in each case, these processes undergo rapid growth and decay cycles.
Attempts to address this issue with hollow fiber bioreactor or other solid bed bioreactor, in which the cells grow attached or entrapped to a fixed surface, are only partially effective; their inherent inhomogeneity and inaccessibility to the cells limits their usefulness as a research tool.
The disadvantage of the bags lies in their inherent fragile nature, limiting their size; although, significant progress has been made in the construction of large disposable bags.
Another disadvantage of the bags is the limited ability to agitate or mix the culture.
Linear scale up of mixing is difficult to sustain with increasing bag size.
While the bag volume increases by the cube, the surface area of the culture head space increases by the square; oxygen transfer becomes limiting as is growth and cell productivity.
There are also limitations on monitoring the conditions of the culture with pH, oxygen or other probes, factors which can profoundly effect the reproducibility of the culture and limit its achievable cell concentration and productivity.
Method used
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Table of Contents of the Detailed Description:
[0047]Detailed description of the enclosed filtration system and process starts: page 16.[0048]Detailed description of the enclosed bioreactor system and process starts: page 40[0049]Detailed description of the manifold system and process starts: page 56.[0050]Detailed description of the dual pump system starts: page 62.[0051]Detailed description of the modifier module system starts: page 76.[0052]Detailed description of the product concentration device, system and process starts: page 85.
Terminology
[0053]“Fluid” that is processed by the reactor systems of the inventions are normally aqueous solutions that may or may not comprise suspended particulate matter (such as cells, cell fragments, non-soluble molecular complexes, particles or soluble molecules). The fluid may or may not contain molecules that are dissolved in the fluid.
[0054]A “selectively permeable barrier” (or selectively permeable wall) is one that will not allow all particul...
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A product concentration device that utilizes a reservoir connected to a hollow-fiber filter element where the reservoir can serve as a container for filtrate emanating from another filtering device, such that product in the reservoir can be stored, concentrated and / or further processed as desired. Enclosed reactor systems, each of at least three chambers, fluid flow between the chambers controlled by selectively permeable barriers, flow controlled by an alternating flow diaphragm pump.
Description
CROSS REFERENCE TO OTHER APPLICATIONS[0001]This application is a Continuation-In-Part (CIP) of PCT Application No. PCT / US2011 / 001485, filed on Aug. 24, 2011, which claims the benefit of U.S. provisional application Ser. No. 61 / 376,810 filed Aug. 25, 2010. The contents of the above PCT application are incorporated herein by reference.FIELD OF INVENTION[0002]The present invention relates to filtration systems. More specifically, the invention relates to filtration systems for biological fluids and products, as well as sampling manifolds, pump systems, and modifying modules useful in such systems.BACKGROUND[0003]Filtration is typically performed to separate, clarify, modify and / or concentrate a fluid solution, mixture or suspension. In the biotechnology pharmaceutical and medical industries, filtration is vital for the successful production, processing and analysis of drugs, diagnostics, chemicals as well as many other products. As examples, filtration may be used to sterilize fluids o...
Claims
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IPC IPC(8): C12M1/00B01D61/14C12M1/26B01D63/02
CPCB01D63/02B01D2313/243C12M29/16C12M29/18B01D2313/131B01D2313/502B01D61/58B01D61/14C12M29/04C12M33/10
InventorSHEVITZ, JERRY
OwnerREPLIGEN CORP